Abstract
The STAT4 gene encodes a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. The aim of this study was to explore the association of STAT4 polymorphism with Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). A total of 1048 autoimmune thyroid diseases (AITDs) patients (693 with GD and 355 with HT) and 909 age- and gender-matched controls were examined. STAT4 polymorphisms (rs7574865/rs10181656/rs7572482) were genotyped by multiplex polymerase chain reaction (PCR) and ligase detection reaction (LDR). The results indicated that the frequencies of rs7574865 genotypes in patients with GD differed significantly from the controls (p = 0.028), the T allele frequency of GD patients was also significantly higher than the controls (p = 0.020). The genotypes of rs10181656 differed significantly in GD patients from controls (p = 0.012); G allele frequencies were significantly higher in AITD patients than the controls (p = 0.014 and 0.031, respectively). The frequencies of haplotype GC with GD and HT patients were significantly lower than their controls (p = 0.015 and 0.030, respectively). In contrast, the frequencies of haplotype TG with GD and HT patients were significantly higher than their controls (p = 0.016 and 0.048, respectively). These findings strongly suggest that STAT4 rs7574865/rs10181656 polymorphisms increase the risk of AITD in a Chinese population.
Highlights
Autoimmune thyroid diseases (AITDs), mainly including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are organ-specific autoimmune disorders
Genotype distributions for single nucleotide polymorphism (SNP) rs7574685, rs10181656, rs7572482 were in accordance with the predicted Hardy-Weinberg equilibrium in both patient and control groups (Table 1)
All the allele and genotypic frequencies of these three SNPs in AITD patients and healthy controls are presented in Tables 2 and 3
Summary
Autoimmune thyroid diseases (AITDs), mainly including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are organ-specific autoimmune disorders. STAT4 belonging to the STAT family expressed in lymphocytes, macrophages, and dendritic cells, encodes a transcription factor that resides in the cytosol. It transmits the intracellular signals induced by cytokines including interleukin-12 (IL-12), IL-23, IL-27 and type-1 interferons (IFNs) [16]. Upon cytokine signaling, this transcription factor becomes phosphorylated and translocates to the nucleus to play an essential downstream role in the differentiation and proliferation of IL-12-dependent T helper 1 (Th1) cells [17]
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